Oxidative stress is the term used to describe a biological state where the production of harmful oxidants by bodily systems or extern sources overwhelms the natural antioxidant defences leading to cellular and tissue damage or destruction. These oxidants may be free radicals or reactive oxygen species, both may be rendered inactive by the natural antioxidant defence systems of the body. Oxidative stress has been implicated as a contributory factor in many diseases, for example atherosclerosis and its consequences, respiratory diseases, arthritis, cancer, diseases of the nervous system, e.g. Parkinson's disease, and of the digestive system, e.g. pancreatitis. Under certain conditions the activity of the immune system may be impaired. Naturally occurring antioxidants include some vitamins e.g. vitamins C and E; some phytochemicals e.g. flavonoids; certain inorganic elements e.g. selenium. These may be incorporated into enzymes that scavenge the oxidant species and render them harmless. These enzymes may be metallo-proteins that incorporate trace elements such as selenium. A typical example is the selenium containing enzyme glutathione peroxidase. Deficiencies in the diet of the amino acid precursors used in the biosynthesis of these enzymes and the essential trace elements or their poor bio-availability, can result in impairment of protective enzymes leading to the signs of oxidative stress.
Acute, recurrent and chronic pancreatitis are common disorders affecting 1 in 20,000 of the adult population of the developed nations, the prevalence in the under developed countries is believed to be higher. The pathogenesis of the forms of pancreatitis is the subject of debate, but chemical insults from xenobiotics and viral infection are implicated in many cases. Both also can cause an increase in free radical production, and it is possible that it is this effect that initiates and perpetuates pancreatitis.
The standard treatment for recalcitrant chronic pancreatitis is a partial pancreatectomy, the cost of which is about .English Pound.12,000. Manchester Royal Infirmary normally perform about 72 such operations per annum. With extrapolation to 20 centres in the whole country, the cost to the National Health Service of this form of treatment is in the region of .English Pound.171/4million per year.
Patients with acute and chronic pancreatitis have been shown to have dietary intakes of antioxidants (Rose et. al. Hum. Nutr. Clin. Nutr.; 40(2); 151-64; 1986), blood levels of ascorbic acid, selenium, .beta.-carotene, vitamin E (Uden et al. Aliment. Pharmacol. Ther.; 6(2); 229-40; 1992) and glutathione that are below normal levels.
Treatment with antioxidant therapy and methionine has resulted in patients showing clinical improvement as demonstrated by a reduction in the degree and severity of symptoms associated with a restoration to normal of the sub-optimal levels of blood micro-nutrients. (Braganza et al. Pancreas; 2(4); 489-94; 1987).
Xenobiotic induced pancreatitis can also be managed with antioxidants (Uden et al. Aliment. Pharmacol. Ther.; 4(4); 357-71; 1990).
In these studies, however, a combination of different product formulations have been used. These have proved unsatisfactory in practice as the poor bioavailability of the selenium has necessitated the use of multiple tablet mixes of up to 24 tablets per day. This is clinically undesirable as many patients with pancreatitis have a disordered digestive system and dysphagia and find it difficult to comply with the dosage regime. Furthermore, as pancreatitis is often accompanied by impaired absorption of nutrients, the bioavailability of the micro-nutrients can be a limiting factor in any attempts to restore their levels to the optimum.
An antioxidative pharmaceutical formulation has now been prepared, which comprises antioxidative micronutrients suitable for alleviating the symptoms of pancreatitis, together with methionine, and which removes the requirement to take large numbers of tablets daily. The novel formulation presents the micro-nutrients in a highly bio-available and safe form.